2013 — 2016 |
Hu, Jian |
K99Activity Code Description: To support the initial phase of a Career/Research Transition award program that provides 1-2 years of mentored support for highly motivated, advanced postdoctoral research scientists. R00Activity Code Description: To support the second phase of a Career/Research Transition award program that provides 1 -3 years of independent research support (R00) contingent on securing an independent research position. Award recipients will be expected to compete successfully for independent R01 support from the NIH during the R00 research transition award period. |
Targeting Glioma Stem Cells by Perturbation of Telomere Maintenance Mechanisms @ University of Tx Md Anderson Can Ctr
DESCRIPTION (provided by applicant): The proposed study is to explore novel therapeutic opportunities to cure malignant gliomas by perturbing telomere maintenance mechanisms in glioma stem cells. Malignant gliomas are highly resistant to treatment largely due to the existence of glioma stem cells (GSCs), which possess inexhaustible ability to self-renew and proliferate. I propose to target GSCs by inhibiting telomerase because GSCs have higher level of telomerase activity than somatic cells and other non-GSC tumor cells. With Aim 1, I will explore GSCs' response to telomerase inhibition with three independent model systems. I will also test whether anti-telomerase sensitizes conventional radiation therapy and chemotherapy in combinatorial therapy regimens. My previous study showed that anti-telomerase will lead to resistance through ALT (Alternative Lengthening of Telomeres) mechanisms, so in Aim 2 I will generate and characterize GSCs that rely on ALT mechanisms and will explore the possibility to target the weakness of ALT in order to prevent the resistance in response to anti-telomerase therapy. More evidence is pointing to the important function of chromatin remodeling factors in the regulation of telomeres, so in Aim 3, I will investigate the mechanisms of telomeric chromatin remodeling in telomerase+ and ALT+ glioma stem cells. The information obtained from this aim will help us understand the natures of ALT mechanisms in the GSC context and provide new therapeutic opportunities to target ALT+ GSCs. This proposed study will help me to form a strong research program, with which I will launch an independent faculty position in an academic/medical research institution. To that end, my immediate goals are to continue sharpening my technical skills in mouse genetics, telomere biology and stem cell biology and expanding my skills in oncogenomics, biostatistics and translational biology. In terms of my career development, I will be devoted to improve my skills on managing lab, mentoring postdocs and students, scientific writing and presentation, and seeking for collaborations, among others, because these skills are all essential for me to land a faculty position and succeed as a PI. MD Anderson Cancer Center (MDACC) and the Ronald DePinho laboratory provide an excellent training environment for me to achieve these goals. Even though Dr. DePinho is President of MDACC now, he still promises to devote 2.5% effort to my training and career development. I have also formed an extraordinary advisory committee composed of Dr. Mien-Chie Huang, Dr. Wai-Kwan Yung and Dr. Junjie Chen. They will not only provide me technical support for my proposed study, but also guide me to look for a faculty position and succeed as an independent investigator. With the help of K99/R00 training grant, I will have a good start to achieve my long term goals, which are to continue exploring basic and translational problems in cancer biology, including telomere biology and cancer stem cell biology, as a lab head in an academic/medical research institute and to contribute in developing novel cancer therapies as a team player by collaborating with other scientists, physicians and pharmaceutical companies.
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0.942 |
2014 — 2017 |
Hu, Jian |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Collaborative Research: Analysis and Solution Methods For Function Robust Optimization Models @ University of Michigan Ann Arbor
The objective of this award is to study a new class of optimization models where general shape constraints specify the function form, and a maximin criterion is used to resolve the function ambiguity. For many data driven decision problems the functions specifying the problem are obtained from the data through model fitting. This model fitting is done based on a presumed form of the function. The decisions are subsequently made by optimizing the fitted functions. In the modeling framework the function set is specified using properties of the function and non-parametric model fitting. Such problems are called function robust optimization problems. Different types of function robust models will be analyzed and algorithms will be developed for solving these models.
If successful, the results of this research will lead to the development of a new class of optimization modeling techniques and algorithms for solving such models. The solutions obtained from such models are expected to be more robust and efficient under data uncertainty when compared to those obtained from the classical known approaches. A general methodological framework that allows ambiguity in the function form will present a significant conceptual advancement to the field of optimization based decision making. Applications of such problems range from topics in management, intelligent control, and engineering design. Experiments will be performed to validate the algorithms, and to compare the properties of the solutions generated from the new modeling technique.
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0.942 |
2015 — 2018 |
Hu, Jian Hausinger, Robert [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Structure, Mechanism and Nickel Metallocenter Assembly of Lactate Racemase @ Michigan State University
With this award, the Chemistry of Life Processes Program in the Division of Chemistry is funding Professors Robert P. Hausinger and Jian Hu of Michigan State University to characterize the structures and functions of enzymes involved in lactate biosynthesis. The enzyme that is the focus of this study, lactate racemase, interconverts two forms of lactic acid, in a deceptively simple, though chemically challenging, reaction. Information gained with these complexes may be used to inform other, studies of enzymes dependent upon nickel metal centers. This research trains postdoctoral researchers in the use of mass spectrometric, structural, spectroscopic, and mutagenesis studies to characterize the enzyme and its helper proteins. These individuals interact with gifted high school students in the High School Honors Science Program and underrepresented undergraduate students in the Charles Drew Science Scholars program, the Increasing Diversity and Education Access to Sciences (IDEAS) program, and the Summer Research Opportunities Program (SROP). Furthermore, information gained from this project is incorporated into ongoing graduate courses entitled "Metals in Biology," "Protein Structure, Function, and Design," and "Integrated Microbial Biology."
This project examines the functional role and biosynthetic pathway of a recently identified pyridinium-3-thioamide-5-thiocarboxylic acid mononucleotide that coordinates nickel as a (SCS)Ni(II) pincer complex and is covalently bound to Lys184 of lactate racemase, LarA. Synthesis of this cofactor requires the accessory proteins LarB, LarC, and LarE of still undefined roles. Planned analyses include investigation of protein bound and free intermediates by mass spectrometry, structural elucidation of these proteins in their various states by x-ray crystallography, spectrophotometric and biophysical analyses of LarA intermediates during catalysis, and in vitro recapitulation of the biosynthetic pathway by supplying the appropriate cofactors. This research is expected to expand understanding of nickel biochemistry and elucidate mechanistic details of oxidation-reduction chemistry involving a tethered, nickel-containing, nicotinic acid cofactor. The (SCS)Ni(II) cofactor represents the first biological example of a pincer complex, well known to inorganic chemists.
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0.943 |
2015 — 2019 |
Hu, Jian |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Zinc Enrichment/Zinc Sensing Mechanism Through the Extracellular Domain of Zip4 @ Michigan State University
? DESCRIPTION (provided by applicant): Zinc is the second most abundant microminerals in humans and is essential for life. Many diseases are associated with abnormal zinc metabolism. Zinc homeostasis in humans is primarily maintained by the adjustments of zinc absorption and excretion through zinc transporters. As one of two major zinc transporter families in mammals, Zrt- and Irt-like proteins (ZIP) facilitate zinc ions flux across membranes from extracellular spac or intracellular organelles into the cytoplasm. The fourteen ZIP proteins in humans share a conserved transmembrane domain (TMD) which forms the ion transport pathway, whereas the variable extracellular domains (ECD) are thought to play regulatory roles associated with the diverse functions of different ZIP proteins. The importance of the ECD is well documented in the study of ZIP4, a representative ZIP protein exclusively responsible for zinc absorption in the intestine. It has been established that missense mutations of ZIP4 cause a lethal genetic disorder, Acrodermatitis Enteropathica (AE), due to severe zinc deficiency. Notably, more than half of the AE-causing mutations of ZIP4 occur within the ECD. Previous biochemical and cell biological studies indicated that ZIP4-ECD plays crucial roles in zinc transport and ZIP4 protein regulation. However, the lack of high resolution three-dimensional structure of ZIP4-ECD prevents incisive structure-function studies. This is a major barrier to the understanding of the underlying mechanism of ZIP4-ECD function and why AE-causing mutations on ZIP4-ECD cause ZIP4 dysfunction and misregulation. In this work, we will focus on the structural and functional study of ZIP4-ECD and our central hypothesis is that ZIP4-ECD is a zinc binding domain and acts as both a zinc trap and a zinc sensor. In Specific Aim1, we will solve the crystal structure of a mammalian ZIP4-ECD. In Specific Aim2, we will characterize zinc binding and zinc binding induced conformational changes in ZIP4-ECD. In Specific Aim3, we will clarify the molecular mechanism of how AE-causing mutations on ZIP4-ECD impair the function and regulation of ZIP4, and establish the structure-function relationship of ZIP4-ECD. This work is significant because establishment of structure-function relationship of ZIP4-ECD will not only advance our knowledge about zinc transport through ZIP4 and the mechanism of ZIP4 regulation, but also promote the study of other ZIP proteins important in medicine. In terms of translational significance, ZIP4-ECD is an attractive drug targeting site and the high resolution structure of ZIP4-ECD will facilitate the design and development of ZIP4 inhibitors and activators. Several lines of evidences strongly suggested that ZIP4 inhibition is a promising strategy against cancer, particularly pancreatic cancer. In contrast, application of an allosteric agonist of ZIP4 may strengthen the effects of zinc supplement to the people at high risk of zinc deficiency, such as pregnant/lactating women and elders, by improving zinc absorption efficiency of ZIP4.
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0.945 |
2018 — 2021 |
Hu, Jian |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. R37Activity Code Description: To provide long-term grant support to investigators whose research competence and productivity are distinctly superior and who are highly likely to continue to perform in an outstanding manner. Investigators may not apply for a MERIT award. Program staff and/or members of the cognizant National Advisory Council/Board will identify candidates for the MERIT award during the course of review of competing research grant applications prepared and submitted in accordance with regular PHS requirements. |
Role of Quaking Gene in Regulating the Niche-Independent Stemness of Glioma Stem Cells @ University of Tx Md Anderson Can Ctr
PROJECT SUMMARY Glioblastoma is the most common type of brain tumor and is currently incurable. The lack of effective treatments highlights the urgent need for identifying mechanism-based therapeutic approaches. Substantial experimental evidence has recently revealed a population of neural stem cell (NSC)-like glioma stem cells (GSCs) that possess an inexhaustible ability to self-renew as the ?root? of glioblastoma. Like NSCs, GSCs are known to maintain their stemness by interacting with niches, which provides proper cues to prevent them from differentiating. But how GSCs manage to sustain their self-renewal capacity in the sub-optimal environment outside the niches, particularly during the process of invasion and migration, remains less clear. As part of our effort to identify potential glioma suppressors involved in the regulation of central nervous system development, we discovered that RNA binding protein Quaking (QKI) is a major regulator of NSC and GSC self-renewal. QKI is frequently deleted or mutated in human glioblastomas. Using a newly established animal model, we genetically demonstrated that QKI is a bona fide glioma suppressor whose depletion strongly promotes gliomagenesis. Functionally, we revealed that QKI is a key regulator of cellular endocytosis that controls receptor trafficking, degradation, and signaling desensitization. Specifically, we showed that depletion of QKI led to the enrichment of cytoplasmic membrane-bound Wnt and Notch receptors (Frizzled and Notch1) and subsequent signal hyperactivation. Given that Wnt and Notch1 are two major signaling cascades involved in maintaining NSC and GSC stemness against differentiation, we propose that QKI modulates NSC and GSC self-renewal and gliomagenesis by controlling endolysosome-mediated Frizzled and Notch1 degradation. To test this hypothesis, in Aim 1, we will determine how QKI regulates the endolysosome-dependent degradation of Wnt receptor Frizzled in NSCs and GSCs. In Aim 2, we will delineate the molecular mechanism by which QKI modulates RNA alternative splicing of the endocytic regulator Numb and the endolysosomal Notch1 degradation. Together, these studies will elucidate the molecular mechanisms underlying QKI-mediated endolysosome-dependent regulation of Wnt and Notch1 signal activation, and more importantly, they will contribute to the development of therapeutic strategies that specifically target QKI-depleted glioblastoma.
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0.942 |
2018 — 2020 |
Hu, Jian |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Structural and Mechanistic Characterization of the Zip Metal Transporters @ Michigan State University
Project Summary Transition metal zinc is the second most abundant trace element in human body and it has been extensively exploited in biological systems for enzymatic catalysis, structural stability and signal transduction. To precisely control the levels of this potential toxic metal, designated transport systems have been evolved. Zinc transport is primarily conducted by the ZnT family for efflux and the Zrt-/Irt-like protein (ZIP) family for influx from either extracellular space or intracellular organelles. The fourteen human ZIPs are broadly involved in a variety of physiological and pathological processes, but little is known about the structure and the transport mechanism of the ZIPs, which hinders the development of novel therapies. Our recent progress of solving the first crystal structure of a prokaryotic ZIP has paved a way towards the ultimate goal of this project - a thorough understanding of the metal transport mechanism of the ZIPs. To achieve this goal, we will focus our research on a prototypical bacterial ZIP and the human protein ZIP4, which is exclusively responsible for zinc uptake from dietary food and involved in genetic disease and cancers, in the following three aspects. In Aim1, we will structurally characterize the outward- facing conformation of the ZIPs by using a combination of structural, computational, biochemical and cell biological approaches. This structural information, together with the previously characterized inward-facing conformation, will enable us to establish an alternating access mechanism in metal transport. In Aim2, we will clarify the roles of the binuclear metal center, which was unexpectedly identified in the middle of the transport pathway, in zinc binding and zinc binding facilitated conformational transition during a transport cycle. The knowledge obtained in Aim1 and Aim2 will help us to depict a full transport cycle. In Aim3, we will identify the molecular determinants of substrate specificity in the human ZIPs. We will make comparison between ZIP4 and ZIP8, whose physiological substrates are zinc and manganese, respectively, and identify the key residues/elements dictating the substrate preference by systematic mutagenesis and activity measurement. Overall, the findings obtained through these efforts will greatly increase knowledge of the unique metal transport mechanism of the ZIPs, which will fill the knowledge gap in zinc signaling and zinc homeostasis, expand the structural and mechanistic diversity of membrane transporters, and importantly, facilitate the development of new therapeutics against human diseases, including several types of cancers.
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0.945 |
2019 — 2021 |
Hausinger, Robert P [⬀] Hu, Jian |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Nickel-Pincer Nucleotide Enzymes @ Michigan State University
Project Summary/Abstract The nickel-pincer nucleotide (NPN) cofactor is a newly identified coenzyme discovered in lactate racemase (LarA) from Lactobacillus plantarum. Synthesis of the active enzyme requires the participation of three accessory proteins that act in sequence: LarB carboxylates the pyridinium ring and hydrolyzes the phosphoanhydride of nicotinic acid adenine dinucleotide, LarE converts the two pyridinium ring carboxylates to thiocarboxylates, and LarC inserts nickel (forming two S-Ni and one C-Ni bonds) during synthesis of the novel cofactor. Genes encoding these four proteins are widely distributed in microorganisms associated with the human microbiome and among human pathogens. The long-term objective of the effort described here is to advance significantly our understanding of how microorganisms, including pathogenic species, make and utilize the NPN cofactor. Two specific aims will achieve this objective: (1) characterize the components of the NPN biosynthetic systems and (2) identify the roles of the NPN cofactor in lactate racemase and additional enzymes. Investigations of LarB will define the structure and mechanism of this pyridinium ring carboxylase/phosphoanhydride hydrolase. Studies of a multi-cysteine and probable [4Fe4S]-containing form of LarE will establish whether it operates by a catalytic sulfur-transfer mechanism, in contrast to the sacrificial LarE of L. plantarum with its single active site cysteine that converts to dehydroalanine. Structural and mechanistic analysis of the CTP-dependent nickel-inserting LarC will elucidate how this protein installs nickel into the cofactor. The geometry of lactate binding to L. plantarum LarA will be defined, the full range of substrates used by this enzyme will be established, and substrates will be identified for alternative LarA-like proteins. Proteins that covalently bind the NPN cofactor will be identified and characterized using innovative chemistry that reacts the coenzyme with a fluorescent tag. Radioactive nickel (63Ni) and 14C-nicotinic acid also will be used to label new NPN cofactor-binding proteins, followed by mass spectrometry, bioinformatics, and biochemical studies to identify the functions of these novel enzymes. The findings obtained through these efforts will greatly increase knowledge of the synthesis and utilization of nickel- pincer cofactors in bacteria, including those important to human health, with implications for identification of potential antimicrobial drug targets.
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0.943 |
2019 — 2025 |
Hausinger, Robert [⬀] Hu, Jian |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Collaborative Research: Ethylene-Forming Enzyme @ Michigan State University
With the support of the Chemistry of Life Processes program in the Division of Chemistry, Robert Hausinger and Jian Hu at Michigan State University and Christo Christov at Michigan Technological University are studying the catalytic strategy of the ethylene-forming enzyme (EFE). This bacterial or fungal protein is a member of the non-heme Fe(II)- and 2-oxoglutarate (2OG)-dependent oxygenases and is distinct from the well-known plant enzyme that also forms ethylene but by a distinct process. EFE catalyzes two distinct reactions, with one producing ethylene and the other generating the nitrogen-rich compound guanidine. Ethylene is the natural plant-ripening hormone and has been advanced as a fuel source alternative to gasoline. Guanidine is a potential nitrogen fertilizer. Thus, the reactions that produce ethylene and guanidine are of fundamental interest and have potential national economic benefits and societal impacts. Investigation of the EFE enzyme will provide advanced training in biochemical, structural, and computational approaches to two postdoctoral scientists and to undergraduate students. Scientific advances obtained from this project will be incorporated into university graduate courses. In addition, the findings from these studies will be communicated to lifelong learners in the general public via presentations at the university Science Festival. <br/><br/>The overarching goal of this proposal is to elucidate the catalytic mechanism of EFE by a combination of experimental and computational studies. Critical to this process are studies that examine the enzyme’s two reactions: (1) decomposition of 2OG into three molecules of carbon dioxide/bicarbonate and ethylene and (2) the conversion of 2OG to succinate and carbon dioxide and transformation of the amino acid L-arginine (L-Arg) into guanidine and L-Δ1-pyrroline-5-carboxylate. To understand the molecular determinants that control the relative activities for the two reactions, biochemical, structural, and computational approaches will be applied to site-directed variants of the best studied EFE from the bacterium Pseudomonas syringae, an EFE homolog from the fungus Penicillium digitatum, and to reconstructed ancestral EFE proteins. Using this information along with structure-guided protein engineering, EFE variants that are optimized for producing the biofuel ethylene or the plant fertilizer guanidine will be created. This work significantly extends the structural/mechanistic information available for other important Fe(II)- and 2OG-dependent oxygenases that are unable to catalyze these reactions.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
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0.945 |
2021 |
Hu, Jian |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Investigating the Role of Dysfunctional Histone H3.3 in Driving Early Neuronal Development and Pediatric High-Grade Gliomas @ University of Tx Md Anderson Can Ctr
Summary Statement/Abstract Pediatric brain tumors are the most common solid tumors in children, with approximately 5000 new cases diagnosed per year in the United States. Around 17% of brain tumors in children age 0?14 years are high-grade gliomas (HGGs), which are currently incurable. The lack of effective treatments highlights the urgent need to identify mechanism-based therapeutic approaches. Substantial experimental evidence has recently revealed that H3.3-G34R?harboring pediatric HGGs (pHGGs) exhibit high genomic instability and high-level expression of neuronal markers, indicating that these tumors represent a distinct subtype of pHGG compared with other types, including the one with an H3.3-K27M mutation. More than 90% of H3.3-G34R gliomas also harbor ATRX loss-of-function mutations. Using a newly established genetically engineered murine model (GEMM), we demonstrated that H3.3-G34R mutation and ATRX deletion in premalignant neural stem cells (PM-NSCs) with the Trp53-/- background could strongly promote gliomagenesis. These tumors exhibit typical features of human H3.3-G34R?harboring pHGGs, so this GEMM provides us with a faithful tool for studying the molecular mechanisms underlying the synergistic effects of H3.3-G34R mutation and ATRX deletion and for identifying novel therapeutic targets. We have found that H3.3-G34R mutation changes histone modifications both locally and globally and leads to high expression of FoxD1 and HoxA1, transcription factors essential for early neuronal development. Given that enrichments of FoxD1 and HoxA1 are associated with worse prognosis in glioma patients, they provide 2 novel therapeutic targets for pHGGs. In addition, we found that ATRX loss leads to ALT activation, which makes tumor cells sensitive to perturbation of their mitochondrial function. On the basis of these observations, we hypothesize that distinctive epigenetic profiles induced by H3.3-G34R mutation and ATRX loss drive gliomagenesis and lead to targetable vulnerabilities involving dysfunctional telomeres and impaired mitochondrial activity. To test this hypothesis, we plan to 1) determine the roles of FoxD1 and HoxA1 in H3.3- G34R?driven gliomagenesis, 2) define the therapeutic vulnerability induced by ATRX deficiency in pHGGs, and 3) elucidate the synergistic effect of H3.3-G34R mutation and ATRX loss on epigenetic reprogramming in gliomas. The completion of the proposed studies will not only fill the gaps in our knowledge of how H3.3-G34R and ATRX loss change the epigenome to lead to normal neuronal development and gliomagenesis, but also? and more importantly?contribute to the development of therapeutic strategies that target pHGGs and provide insights into the role of epigenetic regulation in brain development and gliomagenesis.
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0.942 |
2021 |
Hu, Jian |
R35Activity Code Description: To provide long term support to an experienced investigator with an outstanding record of research productivity. This support is intended to encourage investigators to embark on long-term projects of unusual potential. |
Transport, Substrate Specificity and Regulation Mechanisms of the Zip Transition Metal Transporters @ Michigan State University
Transport, substrate specificity and regulation mechanisms of the ZIP transition metal transporters Abstract Some d-block transition metals (Fe, Zn, Mn, Cu, Co, Mo and Ni) play key roles in catalysis, structural stability of macromolecules, gene expression regulation and cell signaling. Living organisms have evolved systemic and cellular mechanisms to harness the unique chemical properties of beneficial trace elements and meanwhile to avoid toxicity upon overdose or mislocalization. The long-term goal of this research program is to clarify structural and molecular basis of transition metal biology with a current focus on zinc, the second most abundant trace element after iron in human body. Intracellular zinc concentration and subcellular distribution are tightly regulated by coordinated action of zinc buffers/mufflers, zinc storage proteins, zinc-utilizing macromolecules, zinc- responsive transcription factors and two specific zinc transporter families ? the zinc transporter (ZnT, SLC30A) family and the Zrt-/Irt-like protein (ZIP, SLC39A) family. In this MIRA application, our research focuses on the ZIP family which is not only a central player in zinc homeostasis and zinc signaling but also critically involved in Fe and Mn metabolism in humans. As an ancient protein family, the ZIPs are almost ubiquitous in living organisms and play fundamental roles in transitional metal acquisition from environment and distribution/redistribution within the body. In humans, a total of fourteen ZIPs exert distinct biological functions and are associated with a variety of diseases, including several types of cancer. Albeit important biological functions and critical roles in human health, much less is known about the ZIPs when compared to that of the ZnT family. The last several years have witnessed rapid progress in research of the ZIPs made by metal biology community including this research program. In the next five years we are planning to tackle the following three important questions to further the understanding of the ZIPs at molecular level: (1) What is the structural basis of substrate transport through the transporter? (2) Given the distinct substrate preference among the family members, what are the key factors determining substrate specificity? Can substrate preference be fine-tuned through adjusting the identified key factors for potential applications in agriculture and environmental protection? and (3) What is the molecular basis of zinc-regulated post-translational regulation of human ZIPs? Through a combination of structural, biochemical, biophysical and cell biological approaches, we are going to work on representative family members, including a prokaryotic ZIP, the structure of which has provided a structural framework for the entire family, a couple of human ZIPs associated with diseases and undergoing zinc- dependent post-translational regulation, and a plant ZIP critically involved in cadmium uptake from soil and accordingly a potential target for protein engineering. Success of this project will improve the understanding of transport, substrate specificity and regulation of the ZIP transporters, and also shed light on mechanistic studies of many other membrane transporters, particularly those involved in transition metal homeostasis and signaling.
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0.943 |